Brain resuscitation and organ preservation device and method for performing the same

ABSTRACT

The invention discloses methods for preserving organs in brain-dead humans or cadavers which allows additional time for the organs to remain viable such that they may be harvested for subsequent transplantation. This invention also discloses methods for preserving and/or resuscitating organs in live (nonbrain-dead) patients, allowing for additional time to stabilize the patient&#39;s condition. The methods include the steps of instrumentizing (e.g., catheterizing, cannulating, injecting, etc.) the vessels or tissues around the organ, or the organ itself sought to be preserved and/or resuscitated, the body cavity, or cavities of the body, and introducing a temperature-controlled solution to preserve and/or resuscitate the organ(s). The temperature-controlled organ preservation solution includes components such as oxygen carrying agents, antioxidants, tissue damage reversing and protecting agents, carrier vehicles, diluents, nutrients, and anti-coagulating agents. A device which performs this method is also disclosed. This device includes a fluid reservoir, an oxygen tank, a heat exchanger and removable catheter lines.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation-in-part of application Ser. No.08/069,916, filed Jun. 1, 1993, now U.S. Pat. No. 5,395,312, which is acontinuation-in-part of application Ser. No. 07/886,041, filed May 19,1992, now U.S. Pat. No. 5,234,405, which is a Divisional of applicationSer. No. 07/595,387, filed Oct. 10, 1990, now U.S. Pat. No. 5,149,321.

FIELD OF THE INVENTION

The present invention relates generally to treating ischemic and anoxicbrain injuries associated with cardiac arrest. More particularly, thepresent invention provides an apparatus and method for resuscitation ofthe brain and maintenance of viability during trauma or other periods ofdecreased blood flow, allowing the health professional extra time torestore blood circulation and body functions. With the presentinvention, the brain and associated neurologic tissues remain intact,throughout attempts to restart the victim's heart and restorecirculation, allowing the victim increased chances of survival with lesschance of permanent brain damage.

The present invention also provides an apparatus and method forpreserving organs in brain-dead patients or cadavers, which keeps therequisite organs viable for extended time periods. With this invention,the organs may be preserved such that they are suitable for subsequentharvesting and transplantation.

BRIEF DESCRIPTION OF THE PRIOR ART

During cardiac arrest, the heart ceases to pump blood. Subsequently,there is no circulation, and the brain fails to receive freshlyoxygenated blood. Without a steady supply of oxygenated blood, the brainwill cease to function.

Current resuscitation techniques for cardiac arrest have been directedalmost exclusively towards the heart. However, even with methods such ascardiopulmonary resuscitation (CPR), patient survival rates are low. Inhospitals and clinics with advanced CPR and life support systems, thesurvival rate is normally around 14%. Outside of hospital settings, thesurvival rate is about 5%.

Among cardiac arrest victims overall, less than 10% surviveneurologically intact and without significant brain damage. The otherapproximately 90% either die or sustain some neurologic injury fromischemia, (i.e., lack of blood flow to the brain), or anoxia (i.e., lackof oxygen to the brain). Such frequency of neurologic injury occursbecause after cardiac arrest, basic cardiopulmonary resuscitation andadvanced life support techniques, such as CPR, closed heart cardiacchest massage, and electroshock treatments, typically require fifteen totwenty minutes to regain circulation from a failed heart. Reversibleneurologic damage begins as early as four minutes and irreversibleneurologic damage begins as early as six minutes after circulationstops. To combat this potential neurologic injury, initial resuscitationefforts need to be directed toward reviving the brain in addition toresuscitating the heart.

As indicated above, anoxic and ischemic brain injuries from cardiacarrest result in damage to the brain and associated neurologic tissuesafter about four minutes. In contrast, the heart can survive intact upto approximately four hours after cardiac arrest. The short viability ofbrain tissue upon deprivation of oxygenated blood is a result of therequirement of high amounts of nutrients for tissue maintenance. Braintissue uses almost all of the nutrients supplied by the circulatingblood for maintenance and has very little remaining for storage. Absentblood flow to the brain, the small amount of stored nutrients is rapidlyexhausted. Once exhausted, brain oxygen content rapidly depletes. Thisoxygen depletion is traumatic and causes a series of reactions in theoxygen starved brain tissue cells. These reactions produce free radicalions, primarily consisting of the superoxide radical O₂ ⁻. These freeradicals complex with proteins in the brain and associated neurologictissues, altering respiration, energy transfer and other vital cellularfunctions, and irreversibly damaging these tissues.

Prior efforts at resuscitating the brain have involved highly invasivetreatments, intruding physically into the brain itself. Such invasivetechniques are described in U.S. Pat. Nos. 4,378,797 and 4,445,500issued to Osterholm. These patents describe a stroke treatment methodwhich is a direct physical intrusion into the brain itself. In thismethod, an opening is drilled directly through the skull through thebrain into the pons or brain ventricles. These areas are then directlycannulated and flooded with room temperature oxygenatedperfluorocarbons. These entering perfluorocarbons mix with cerebralspinal fluid, whereby they are carried throughout the brain andassociated neurologic tissues through channels within the centralnervous system, sometimes referred to as the "third circulation." Excessfluid is drained through an opening invasively placed in the cisternamagna of the brain.

This stroke treatment method has several drawbacks. This method must beperformed in a surgical environment by a skilled surgical team. Itcannot be done by a single person with basic medical training. It cannotbe done in the field or other emergency type settings. The device usedin performing this stroke treatment is not portable. Additionally, sincethis procedure is invasive (drilling directly into the brain), there isa high risk of mechanical damage to the brain and associated neurologictissues. Finally, the treatment fluid used contains essentiallyperfluorocarbons. It lacks any agents needed to inhibit free radicaldamage.

Additionally, despite the dramatic success and increase in the number oforgan transplants, there remains a massive shortfall of organs suitablefor donation and subsequent transplant. The demand for organs remainsgreater than the supply. As a result, thousands of people unnecessarilydie.

This is an irony because of the potential abundance of suitable organs.Specifically, more than 1.5 million Americans who die from trauma,accidents or cardiac arrest with organs suitable for transplant, couldeasily have their organs salvaged.

Present salvaging techniques include putting the organ in ice afterhaving been perfused in a Collins solution. This Collins solution mimicsthe internal environment of the cells, which form the organ tissue, andkeeps the organ viable for approximately forty-eight hours. In mostcases, these present methods do not permit sufficient time to transfer asuitable viable organ to the needy recipient. This is because organsdeprived of oxygen nutrient rich blood flow in a body at normal bodytemperature suffer irreversible damage and injury in just a few hours orless. For example, the heart must be salvaged almost immediately, whilethe kidneys must be salvaged within one to three hours.

Under present circumstances, the time prior to that which a potentiallytransferable organ may be salvaged is usually delayed. This occursbecause the brain-dead person must first be brought to a hospital.Alternatively, a person dying outside a hospital or other clinicalsetting must first be brought to a morgue and be pronounced dead. Thefamily must then sign organ donation forms. Only after the brain-deadperson has been brought to a hospital and the organ donation proceduresare complete, may a surgical team be permitted access to the body toharvest the viable organs for transplant. This procedure takes time to apoint where organs are irreversibly damaged or are no longer viable.

It is therefore an object of this invention to non-invasively treatischemic and anoxic brain injuries immediately upon cardiac arrestwhereby resuscitation efforts are applied in time for a patient tosurvive neurologically intact. By directing resuscitating efforts toimmediately treating the brain, the present invention allows medicalpersonnel substantial additional time (beyond the critical four minutewindow) to regain the failed heart's circulation without the patientsuffering neurologic damage.

It is also an object of the invention to provide a method of treatingischemic and anoxic brain injuries suffered upon cardiac arrest so as toinhibit free radical chemical species from complexing with proteins inthe brain and neurologic tissue to avoid permanent irreversible damage.

It is another object of the invention to resuscitate the brain byestablishing a non-invasive, artificial circulation of syntheticallyoxygenated blood to the brain.

It is yet another object of the invention to prevent and reversepotential damage to the brain and associated neurologic tissue sufferedas a result of ischemic injury due to cardiac arrest, major trauma,suffocation, drowning, electrocution, blood loss and toxic poisoningfrom substances including carbon monoxide and cyanide.

It is a further object of the invention to provide a device for treatingthe aforementioned injuries, which is suited for field as well asclinical use and that can be operated by a single person with minimalmedical training and experience.

It is still another object of the invention to provide a solutioncapable of inhibiting free radical ions from complexing with proteins inbrain and associated neurologic tissue, and capable of protecting thesetissues and reversing injuries to these tissues, thereby expanding thebrain's critical four minute viability window.

It is still another object of this invention to provide a method ofpreserving organs in their viable states in brain-dead patients orcadavers, in order for organ harvesting, whereby the harvested organsare suitable for transplantation.

It is still another object of the invention to prevent and reversepotential damage to a brain-dead patient's or cadaver's organs prior toorgan harvesting such that the harvested organs remain viable forharvesting, whereby they are suitable for transplantation.

SUMMARY OF THE INVENTION

The present invention focuses on initial resuscitation efforts towardresuscitating the brain due to its short viability, rather than theheart. The invention includes a non-invasive method which reverses andinhibits neurologic damage, and resulting ischemic and anoxic injuryupon cardiac arrest. The method includes establishing an artificialcirculation by catheterizing the circulatory system in both externalcarotid arteries, to deliver essential treatment components in asynthetic brain resuscitation solution to the brain. Once catheterized,the brain is driven into a submetabolic coma as barbiturates areintroduced through the catheter. This coma lowers the brain's metabolismand decreases free radical production, while keeping its tissues viable.The brain is oxygenated by introducing temperature-controlledperfluorocarbons, which are supersaturated with oxygen. Theseperfluorocarbons act as a blood substitute and transport oxygen in amanner similar to hemoglobin. Free radical damage is inhibited byintroducing antioxidants, free radical scavengers. The antioxidantscomplex with the ionic O₂ ⁻ and prevent the ions from complexing withproteins in brain tissue, which is a cause of irreversible damage.Protecting and reversing neurologic damage is accomplished byintroducing Lazaroids, an experimental drug class now being developed bythe Upjohn Pharmaceutical Company of Kalamazoo, Mich.

All of the above-mentioned compositions are included in a single brainresuscitation solution. This brain resuscitation solution is deliveredto the brain in a chilled condition. The fluid is chilled by cooling itto a temperature sufficiently low to hypothermically shock the brain. Atthis point, the brain's metabolism is slowed and free radical productiondecreases. The brain is additionally cooled externally with natural orsynthetic ice packs around the patient's head.

Once the procedure is complete, continuing efforts are then made toresuscitate the heart and restore the circulation. This can be achievedby drug administration, CPR (manual and mechanical), chest compression,and the like.

Additionally, the present invention discloses a method of resuscitatingor preserving organs (collectively known as organ preservation) in abrain-dead patient or cadaver prior to their harvesting for transplant,such that a viable organ is transplanted. The method includesestablishing an artificial circulation within the organ by catheterizinga major blood or lymph vessel supplying the organ or organ tissueparenchyma, to deliver essential treatment components in a syntheticsolution to it. The solution is cooled below body temperature andintroduced through the catheter. The solution includes components whichserve to lower the organ's metabolism and decrease free radicalproduction, while keeping the organ viable. Specifically, one suchsolution includes temperature-controlled perfluorocarbons, which aresupersaturated with oxygen. These perfluorocarbons oxygenate the organby acting as a blood substitute, transporting oxygen in a manner similarto hemoglobin. Free radical damage is inhibited by introducingantioxidants, free radical scavengers. The antioxidants complex with theionic O₂ ⁻ and prevent the ions from complexing with proteins in thetissue, which is a cause of irreversible damage. Further tissue damageprotection is accomplished by introducing Lazaroids, an experimentaldrug class now being developed by the Upjohn Pharmaceutical Company ofKalamazoo, Mich.

All of the above-mentioned compositions are included in a solutionsimilar to that described above for brain resuscitation. The onlysignificant difference is that barbiturates, which induce a coma in thebrain, while permissible, are preferably not used in organ preservationas this result is not needed in this instance. Similar to theabove-mentioned brain resuscitation solution, the organ preservation andresuscitation solution (hereinafter organ preservation solution), ischilled by cooling it to a sufficiently low temperature to inhibitdegenerative metabolism of the organ. When the organ's metabolism isslowed, free radical production decreases.

Once this procedure is complete the organ will remain viable, such thatharvesting and subsequent transplantation may take place at a latertime. The harvested organ will have sustained minimal, if any damage,and the transplant recipient will be able to resume a normal life.

The present invention includes a device for delivering theaforementioned brain resuscitation or organ preservation solutions. Thedevice can be adapted for clinical or field use. This device includes areservoir for holding brain resuscitation or organ preservation solutionwhich communicates with an oxygen tank and a heat exchanger. Uponactivation, the oxygen is released into the reservoir, oxygenating thebrain resuscitation or organ preservation solution. The oxygenatedsolution is then pumped from the reservoir to the heat exchanger, whereit is cooled. When brain resuscitation is desired, the cooled solutionis then introduced to the patient's circulatory system through thecatheterized carotid arteries or other blood vessels and directed towardthe brain. Alternately, in organ preservation, the cooled solution isintroduced into blood or lymph vessels supplying the organ, the organitself or the tissue surrounding the organ. For example, with thepancreas, the intestine, a surrounding tissue, would provide organpreservation solution to the pancreas by capillary circulation.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of the invention reference should bemade to the drawings wherein:

FIG. 1 is a front view of the portable brain resuscitation/organpreservation device of the invention illustrating the internalcomponents;

FIG. 2 is a side view of the portable brain resuscitation/organpreservation device of FIG. 1;

FIG. 3 is a front view of a second embodiment of the portable deviceshown in FIG. 2;

FIG. 4 is a flow chart of the method of the present invention; and

FIG. 5 is a front view of the patient being catheterized and;

FIG. 6 is a flow chart of an organ preservation and resuscitation methodof the present invention.

DETAILED DESCRIPTION OF THE DRAWINGS

Referring to FIGS. 1 and 2, the brain resuscitation/organ preservationdevice 20 of this embodiment of the invention is semi-automatic. Itincludes an outer casing 22 with a handle 23 and a window 24. The window24 is located within a first side 25 which has a greater width thanlength. The casing 22 includes an inner chamber 26. This inner chamber26 contains components which include a reservoir 30, an oxygen tank 34,a heat exchanger 38, a pump 46, a logic control unit 50, and a powersource 54.

The reservoir 30 holds the brain resuscitation or organ preservationsolution. The solution of this invention is a fluid mixture of variouscomponents and is packaged in premixed, premeasured canisters, for asingle immediate use. These canisters can be replenished (refilled) andexchanged for continued life support. The specific components arediscussed below in accordance with the methods of the invention.Preferably, this reservoir 30 is adapted to hold three liters of fluidcontained within replaceable canisters 32. The preferred canisters areclear plastic bags, such that fluid depletion in the reservoir 30 can beviewed through the window 24. However, these canisters can be rigidcontainers, made of opaque material.

An oxygen tank 34, adjustable to various pressures, communicates withreservoir 30 through a first conduit 35. Oxygen tank 34 is sealed by avalve 36, which is opened once the device 20 is activated. Tank 34 ispreferably a cylinder ten inches tall by four inches in diameter,containing oxygen pressurized to at least 17 psig.

A heat exchanger 38 capable of controlling the fluid's temperature,surrounds reservoir 30. Preferably the heat exchanger cools byundergoing an internal endothermic reaction, once a charging valve 40 isopened when a charging handle 41 on the device is activated. Theexchanger contains Ammonium Nitrate and water, which are initiallyseparate. Upon activation, these chemicals contact each other, reactingendothermically, causing the heat exchanger to cool. Additionally, theheat exchanger's cooling can be accomplished by carbon dioxide (dryice), freon or a mechanical cooling device.

A second conduit 44 extends from the reservoir and communicates with avalve controlled pump 46, capable of pumping at various rates,directions (forward and reverse) and modes, in communication with alogic control unit 50. The pump 46 and the logic control unit 50 areboth powered by an energy source 54. However, the device is suitable foran electric adapter. A battery pack is the preferred energy source 54.The logic control unit 50 includes (not shown) an oxygen pressuresensor, a fluid mass flow sensor, a fluid volume indicator andregulator, a fluid pressure indicator and regulator, a fluid temperatureindicator and regulator, a fluid temperature indicator with feedback toa mass sensor, and a timing device for estimating the time the fluid inthe reservoir will be depleted at a given mass flow. The logic controlunit 50 can control the rate, direction and mode of pumping, i.e.forward or reverse, continuous or pulsatile. One example of a pulsatilerate and mode would be that which simulates the pulsed flow of a beatingheart. Measurements from logic control unit 50 are displayed on an LEDdigital display 56. Digital display 56 preferably shows the temperatureand flow rate of the brain resuscitation solution.

The second conduit 44 extends through the pump 46 and logic control unit50 and terminates in a side opening 58 on the device 20. Preferably,this side opening 58 is on the side 66 adjacent to the longitudinal side25. Side opening 58 is capable of attaching to catheter lines 60 topermit brain resuscitation solution to enter the patient's circulatorysystem, through catheters 62 placed into a single, but preferably both,external or internal carotid arteries. Similarly, side opening 58 iscapable of attaching to catheter lines 60 to permit organ preservationsolution to enter the patient's circulatory system, through catheters 62placed into a single vessel near the organ sought to be preserved, theorgan itself or tissues surrounding the organ.

With respect to catheters 62, one way balloon tipped catheters arepreferred. The balloons generally inflate upon activation to blockpotential reverse blood and brain resuscitation or organ preservationfluid flow toward the heart (except in organ preservation where theheart is being resuscitated and/or preserved). Catheters 62 may also bedual or multiple lumen catheters. Additionally, it is preferred thatthis adjacent side 66 also contain openings for venting excess oxygen 68and for oxygen intake 69. This oxygen intake can be from the atmosphereor from adjunct oxygen sources.

Upon activating the brain resuscitation or organ preservation device,the oxygen tank valve 36 opens and pressurized oxygen is released fromthe oxygen tank 34 into contact with the brain resuscitation or organpreservation fluid, thereby oxygenating it. The heat exchanger 38 isactivated by releasing the charging valve 40. Once activated, theoxygenated solution in the reservoir is cooled. This cooled solutionmoves through a second conduit 44, drawn by sufficient pressure from theoxygen tank 34 into a logic control unit 50, powered by an energy source54, such as a battery pack. A pump 46, within this logic control unit 50further moves the chilled oxygenated solution through this secondconduit. Solution then enters a catheter line 60, attached to an opening58 in device 20 whereby it is delivered to the brain or organ throughthe catheters 62.

The preferred embodiment of the brain resuscitation/organ preservationdevice 20 is relatively small. It is portable, suitcase-like inappearance, and suitable for field use, such as in ambulances,battlefields, athletic fields, aircraft, marine vehicles, spacecraft,emergency treatment facilities, and the like. It is lightweight and canbe carried directly to the patient. In one example of the device theouter casing measures twenty inches by eighteen inches by fifteen inchesand weighs approximately thirty pounds.

FIG. 3 is a second embodiment of the brain resuscitation/organpreservation device 70. This embodiment is mechanical. It is manuallyactivated and is fully operative under pneumatic power generated bypressurized oxygen. Device 70 includes an outer casing 72 with a handle73 and preferably a window 74, located in a first side 75 having agreater length than width. The outer casing 72 includes an inner chamber76. This inner chamber 76 contains components which include a reservoir80, an oxygen tank 82, a heat exchanger 90, and a logic control unit 96.

The reservoir 80 holds the brain resuscitation or organ preservationsolution of the invention. The brain resuscitation or organ preservationsolution is a mixture of various components and is packaged in premixed,premeasured canisters, for a single immediate use. These canisters canbe replenished (refilled) and exchanged for continued life support. Thespecific components of the brain resuscitation or organ preservationsolution are discussed below in accordance with their respectivemethods. Preferably, reservoir 80 is adapted to hold four to ten litersof solution contained within replaceable canisters 84. The preferredcanisters are clear plastic bags through which the fluid depletion inthe reservoir 80 can be viewed through the window 74.

Reservoir 80 communicates with an oxygen tank 82 through channels 85,which open when a charging handle 86 is pulled. Oxygen tank 82 isadjustable to various pressures and is sealed by a valve 88 on thecharging handle 86. The oxygen is pressurized to at least 17 psig.

Reservoir 80 also communicates with a heat exchanger 90, capable ofcontrolling the solution's temperature, through a conduit 92. Similar tothat of the first embodiment, the preferred heat exchanger cools byundergoing an internal endothermic reaction, as explained with the firstembodiment above. Heat exchanger 90 communicates with the charginghandle through a valve 94, which when activated by pulling, initiatescooling.

Conduit 92 extends through the heat exchanger 90 into a logic controlunit 96. Logic control unit 96 includes (not shown) an oxygen pressuresensor, a fluid mass flow sensor, a fluid pressure indicator and valve98 for regulating fluid pressure and flow, a fluid temperature indicatorand regulator, a fluid temperature indicator with feedback to a masssensor, and a timing device for estimating the time fluid in thereservoir 80 will be depleted at the current mass flow. Measurementsfrom this logic control are displayed on an LED digital display 99.Digital display 99 shows the brain resuscitation or organ preservationfluid temperature and flow rate.

Conduit 92 extends from the logic control unit 96, to a terminal point100 outside the device 70. A high pressure fluid coupling valve 102 isat this terminal point 100. The valve 102 is opened when the device 70is activated. This terminal point 100 is suitable for attachment ofcatheter line 104 and subsequent catheters 106.

As with device 20, one way balloon tipped catheters are preferred inalternate device 70. Upon activation the balloon portion of the catheterinflates, blocking possible reverse blood and brain resuscitation ororgan preservation solution flow toward the heart. Additionally, it ispreferred that device 70 contain openings for venting excess oxygen andfor oxygen intake. This oxygen intake can be from the atmosphere oradjunct oxygen sources.

Device 70 is activated when the user pulls the charging handle 86. Thisaction opens a valve 88 on the oxygen tank 82, releasing pressurizedoxygen, which moves through channels 85 into the reservoir 80 and intocontact with the brain resuscitation or organ preservation solutionthereby oxygenating the fluid solution. The pressure from this releasedoxygen drives the oxygenated solution into conduit 92 which passesthrough a heat exchanger 90, thereby cooling the solution. Once thecooled oxygenated fluid solution leaves the heat exchanger 90, itcontinues in conduit 92 through the logic control unit 96.

Once past the logic control unit 96, the solution moves through thisconduit 92 until it terminates in a high pressure solution couplingvalve 102 outside of the device 70. When the high pressure valve 102 isopen, and catheters 106 are coupled to this terminal conduit end 100,brain resuscitation or organ preservation solution can enter thepatient's circulatory system. The oxygen pressure preferred is at least17 psig, sufficient to drive this brain resuscitation or organpreservation solution from the reservoir 80 into the brain or organrespectively.

Other alternative embodiments may have two reservoirs. This would beespecially useful in brain resuscitation. The first reservoir would bekept at body temperature or slightly cooler whereby this "warm" brainresuscitation solution is available to flood the brain and quicklydiffuses in it, whereby the blood-brain barrier is crossed. The secondreservoir is available to deliver "cool" (approximately forty degreesfahrenheit) resuscitation solution, chilled by the heat exchanger, forthe purpose of inducing hypothermic shock (discussed below).

Another alternative embodiment of the two-reservoir device, quiteadvantageous for brain resuscitation, includes a first reservoircontaining unoxygenated fluid, kept at body temperature or slightlybelow. A bolus of this "warm" unoxygenated solution is initiallydelivered to the brain, so as to prevent an oxidative burst of freeradicals. The second reservoir is available to deliver cool(approximately 40 degrees F.) oxygenated resuscitation solution to thebrain for the purpose of inducing hypothermic shock (discussed below).The above-described heat exchangers cool the solution, while oxygenatingthe solution occurs through either of the embodiments disclosed in FIGS.1-3, as either of these embodiments is modified such that only thissecond reservoir communicates with the oxygen source. The "cool"oxygenated resuscitation solution is delivered to the brain shortlyafter the initial "warm" unoxygenated solution has been delivered.

Still additional alternative embodiments may use preoxygenated solutionin the reservoirs. Reservoirs containing preoxygenated fluid solutioneliminate the need for oxygen tanks as these devices have sufficientpower (enhanced electronics and powerful pumps), capable of moving thebrain resuscitation solution from the reservoir in the device to thebrain.

While these two preferred embodiments are portable devices particularlysuited for portable, field use, they are also suited for stationary,clinical use. Should a clinical device be desired, these two portableembodiments could be made larger and modified accordingly for such use.

In operation, the brain resuscitation/organ preservation device suppliestreatment solution for the accompanying resuscitation or preservationmethods respectively. As previously stated, one aspect of the inventioncomprises a method of treating anoxic and ischemic injuries suffered asa result of cardiac arrest, suffocation, drowning, electrocution, lossesof circulation, strokes, bodily injuries, toxic (carbon monoxide,cyanide, etc.) poisoning, and associated major trauma.

Reference is now made to FIGS. 4 and 5 which describe and show thenon-invasive method of the invention for brain resuscitation.Preferably, this method involves the initial step of shunting alleffective cardiac output away from the lower extremities and the abdomen112 and toward the patient's heart and head at step 112. This shuntingis preferably accomplished with mast trousers or pneumatic compressionsuits, which compress the lower abdomen and lower extremities forcingblood to the heart. However, other equivalent devices may be employed.During this time, the patient's lungs are ventilated with 100% oxygenalong with basic cardiac life support or chest percussion andventilation at step 114.

An artificial circulation through the brain is established at step 116as the patient 118 is catheterized at an injection point along thecirculatory system 120. The brain resuscitation solution enters thecirculatory system through at least one blood vessel (artery or vein).Preferably, at least one external or internal carotid artery iscatheterized. These carotid arteries are preferred since they are largearteries leading directly to the brain and can be easily found byfeeling for the carotid pulse. Alternatively, any other blood vessel(artery or vein) may be the injection point catheterized. Such pointsinclude the femoral arteries, or jugular veins.

Balloon type catheters 121 with one way balloon valves at a distal pointare preferred. Once inserted into the arteries, the balloons inflate,limiting any reverse blood and brain resuscitation fluid solution flowtoward the heart through the artery.

Prior to catheterization, the catheter lines 122 are attached to thebrain resuscitation device. This device is now activated andtemperature-controlled (chilled) oxygenated brain resuscitation solutionis delivered to the brain at step 124. This brain resuscitation solutionis a mixture of various components suitable for treating these ischemicand anoxic injuries and keeping the brain and associated neurologictissues intact. Specifically, the brain resuscitation solution is afluid mixture containing barbiturates, oxygen carrying agents,antioxidants, Lazaroids, carrier vehicles, nutrients and otherchemicals.

Initially the solution is temperature controlled, and delivered to thebrain after having been chilled to approximately forty degrees F. Atthis temperature, the brain is hypothermically shocked and itsmetabolism, and subsequent free radical production is slowed. Thistemperature-controlling (cooling) step 124 may alone allow an additionalthirty minutes of brain viability. Additional cooling is achieved byapplying external cooling means to the patient's head. The cooling meansincludes bonnets containing ice cubes, synthetic cooling packets and thelike. These bonnets may extend to cover the neck and spinal column.

Barbiturates comprise from about 0.000 to 20.00 percent by volume of thebrain resuscitation solution. Preferably, the brain resuscitationsolution includes 0.001 to 10.00 percent by volume of barbiturates.These barbiturates drive the brain into a submetabolic coma at step 126.Brain metabolism and subsequent free radical production are furtherlowered.

Thiopental is the preferred barbiturate. It has a fast induction time asit can cross the blood-brain barrier in three to seven seconds.Alternately, Secobarbital or Pentobarbital may be used.

Oxygen carrying agents comprise from about 0.00 to 99.90 percent byvolume of this brain resuscitation solution. The preferred brainresuscitation solution includes 10.00 to 99.90 percent by volume ofoxygen carrying agents. Perfluorocarbons are the preferred oxygencarrying agents, as they have an extremely high oxygen carryingcapacity. When delivered to the brain, in this oxidation step 128, theseperfluorocarbons are supersaturated with oxygen, having been oxygenatedin the fluid reservoir. These perfluorocarbons act as a bloodsubstitute, carrying oxygen to the brain similar to hemoglobin in theblood. These perfluorocarbons are temperature controlled and enter thepatient's circulation at temperatures between 0 and 105 degrees F.

Antioxidants comprise from about 0.00 to 50.00 percent by volume of thisbrain resuscitation solution. Preferably, the brain resuscitationsolution includes 0.001 to 30.00 percent by volume of antioxidants.These antioxidants are the preferred free radical scavengers. Onceintroduced into the brain at step 130, these antioxidants compete withbrain tissue proteins as binding sites for the free radicals, mainlyionic O₂ ⁻. Since a large portion of the free radicals complex withantioxidants, a substantial amount of free radical damage is preventedsince these same free radicals do not bind and form complexes withproteins in the brain and associated neurologic tissues. The preferredantioxidants include Vitamin A, Vitamin B, Vitamin C, Vitamin E,Selenium Cystine, Cysteine, BHT, BHA, Hydergine and the like.

Lazaroids, an experimental drug class being developed by the Upjohn Co.of Kalamazoo, Mich., comprise about 0.00 to 30.00 percent by volume ofthe brain resuscitation solution. Preferably, Lazaroids comprise 0.001to 20.00 percent by volume of the brain resuscitation solution. TheseLazaroids are the preferred agents for protecting and reversing anoxicbrain injury for up to forty-five minutes of anoxia, as shown in animalstudies. These Lazaroids as well as nutrients, are introduced to thebrain at step 132 in the brain resuscitation solution. Lazaroids arealso free radical scavengers which fall under two major root moieties:pregnanes, ranging in molecular weight from roughly 580-720 andbenzopyrans, ranging in molecular weight from 425-905.

The brain resuscitation solution may include up to 50 percent by volumeof components which act as carrier vehicles and diluents for theantioxidants, barbiturates, perfluorocarbons and Lazaroids.Dimethylsulfoxide (DMSO) is the preferred carrier as it aids the aboveagents in traversing brain cell membranes. Additionally, the brainresuscitation solution may contain physiologic buffers to maintain pH.

Nutrients are also provided in this solution, up to 30 percent byvolume. Glucose is one nutrient which is preferred.

Finally, the solution may contain up to 10 percent by volume of heparinor other suitable anti-blood coagulating agents to stop blood clottingwhich may occur due to lack of blood flow during the resuscitationattempt as a side effect of arterial system blockage and fluid backflowfrom the balloon tipped catheter.

Once this method has been performed and the brain resuscitation fluidhas been properly administered, continuing efforts to restart the heartand restore the circulation at step 134 should be made.

Alternately, a method exists for use in emergency situations. In thesesituations, preoxygenated fluid may be directly injected into thepatient's circulatory system. This is done by removing the reservoircanister from the brain resuscitation device and attaching it to acatheter line and then catheterizing the patient's circulatory system,or placing fluid from the reservoir canister into a syringe andinjecting the patient.

The invention additionally discloses a method for preserving organs suchas the heart, lungs, kidneys, pancreas and liver whereby they remainviable and suitable for harvesting and subsequent transplantation, inbrain-dead patients or cadavers. This method can also be used to treatlive (nonbrain-dead) patients, to preserve and resuscitate their organs.For example, these live patients may be suffering from ischemic injuriesor other metabolic insults due to cardiac arrest, major trauma,suffocation, drowning, electrocution, blood loss and toxic poisoningfrom substances including carbon monoxide and cyanide.

The method involves establishing an artificial circulation for organpreservation and resuscitation solution (hereinafter "organ preservationsolution") through the organ to be harvested (or preserved and/orresuscitated as with a live patient), as the patient is catheterized atan injection point. This injection point typically includes a majorblood or lymph vessel, the organ itself, or tissues surrounding theorgan. If a lymph vessel is catheterized, it should be in closeproximity to the organ to be harvested. Preferably, arteries proximateto the organ are catheterized, as they can be found easily and provide adirect route to the organ.

Balloon-type catheters (similar or identical to those disclosed above)with one-way balloon valves at a distal point are preferred. Onceinserted into the vessels of the circulatory system, the balloonsinflate, limiting any reverse blood flow and organ preservation solutionflow away from the organ to be harvested.

The invention also provides a method for preserving and/or resuscitatingorgans such as the heart, lungs, kidneys, pancreas, liver, intestines,stomach, esophagus and the like, whereby they remain viable and sufferminimal damage. The invention may be used to treat live patients, whosuffer ischemic injury or other metabolic insults due to cardiac arrest,major trauma, suffocation, drowning, electrocution, blood loss and toxicpoisoning from substances including carbon monoxide and cyanide. It mayalso be used on brain-dead patients and cadavers, such that the organswould remain viable and suitable for harvesting and subsequenttransplantation. This method involves the direct perfusion of bodycavities such as the abdomen (abdominal or peritoneal cavity) and thorax(thoracic or chest cavity). This perfusion method involves filling thebody cavities with the organ preservation solutions (disclosed below).The perfused organ preservation solution reaches the organs, tissues orvasculature associated with the organs through diffusion and/or otherfluid adsorption processes.

The invention further provides a method for preserving and/orresuscitating organs such as the heart, lungs, kidneys, bladder,pancreas, liver, intestines, stomach, esophagus and the like, wherebythey remain viable and suffer minimal damage. The invention may be usedto treat live patients, who suffer ischemic injury or other metabolicinsults due to cardiac arrest, major trauma, suffocation, drowning,electrocution, blood loss and toxic poisoning from substances includingcarbon monoxide and cyanide. It may also be used on brain-dead patientsand cadavers to preserve the organs, such that they would remain viableand suitable for harvesting and subsequent transplantation. This methodinvolves the direct infusion of cavities of the body, such as thegastro-intestinal (GI) tract, the respiratory tract, the urinary tract,the oral cavity, the nasal and sinus cavities, and any other spaces inthe body in which fluid can be placed. This infusion method involvesfilling the cavities of the body with the organ preservation solutions(disclosed below). Entry into these cavities of the body is typicallythrough body orifices, such as the mouth, nose, rectum, or urethra. Theinfused organ preservation solution is directly absorbed into the organsalong the respective tracts as well as through diffusion and/or otherfluid adsorption processes.

With body cavity perfusion, catheters, including the balloon typecatheters and dual lumen (or multiple lumen) catheters disclosed above,specially designed catheters, tubes, cannulas, trocars, syringes,needles, or any equivalent delivery instruments may be used toinstrumentize and deliver the organ preservation solutions (disclosedbelow) to perfuse the selected body cavity. The instrumentization(catheterization, cannulation or injection) involves piercing the skinat any point about the abdominal or thoracic cavities.

As with infusion of cavities of the body, catheters, including theballoon type catheters and dual lumen (or multiple lumen) cathetersdisclosed above, specially designed catheters, cannulas and tubes, suchas nasal-gastric tubes, GI tubes, endotracheal tubes, or any equivalentdelivery instruments may be used to instrumentize and deliver and infusethe organ preservation solutions (disclosed below) into the selectedtracts (cavities of the body). Infusion is through any body orifice(e.g., mouth, nose, rectum or urethra) or passageway.

Reference is now made to FIG. 6. The organ preservation solutions(disclosed below) may be delivered to the body (perfused into bodycavities or infused into cavities of the body), step 212, through theabove-listed instruments (e.g., catheters, cannulas, needles, tubes,syringes, trocars, etc.), that are attached to the side opening or theterminal point of the organ preservation devices (disclosed above), fromthe reservoirs in the organ preservation devices. Once the devices areactivated, delivery of temperature-controlled (chilled) oxygenated ornon-oxygenated (unoxygenated) organ preservation solutions (step 224),for the above-disclosed methods, begins. The organ preservationsolutions (disclosed below) are a mixture of various components suitablefor keeping the organ(s) and tissues viable (and also resuscitating theorgans in live, nonbrain-dead patients). Specifically, the organpreservation solutions are fluid mixtures that may include componentssuch as oxygen carrying agents (step 228), antioxidants (step 230),Lazaroids (step 232), carrier vehicles, nutrients, cytoprotective agentsand other chemicals. It is similar to that disclosed above for brainresuscitation except that barbiturates, which may be included, are notrequired as there is not a great need to induce a coma in a brain-deadpatient or cadaver, nor a live patient here.

In the organ preservation methods disclosed above, the solution istemperature-controlled and delivered to the organ(s), tissues orvasculature associated with the organ(s), the body cavities (perfusion),or cavities of the body (infusion), after having been chilled belownormal body temperature which may be to approximately 40 degrees F. Attemperatures below normal body temperature, the degenerative metabolismof the organ(s) is slowed as the subsequent free radical production (O₂⁻ or other free radicals) decreases. This temperature-controlling(cooling) step 224 may alone allow up to an additional four hours oforgan viability. The delivery of the chilled organ preservation solutionmay be continuous or pulsatile, cyclic or non-cyclic, depending upon thetype of pump and logic control unit and organ preservation device(disclosed above).

With respect to pulsatile delivery, for the organ preservation methodsdisclosed above, the pump on the organ preservation device may becontrolled to pump in both the forward and reverse directions. Bypumping in both directions, organ preservation solution either 1)delivered into the major blood or lymph vessels, the organ itself, ortissues surrounding the organ, 2) delivered into the body cavity (i.e.,perfusion), or 3) delivered into cavities of the body (i.e. infusion),could be returned through the catheter (or other similar cannula, tubeor instrumentation) to the reservoir. Solution would then be returnedfrom the reservoir to the organ(s), tissues or vasculature associatedwith the organ(s), the body cavities, or the cavities of the body,through subsequent pumping in a cyclic manner, for as long as desired.The combination of pulses from the pump could be determined by theoperator of the organ preservation device, such that optimal circulationis based upon the volume and pressure capacity of the organ(s), the bodycavity (as with body cavity perfusion), or cavities of the body (as withinfusion).

For example, the pump could deliver a preset fluid volume, fluid at apreset pressure, or fluid at a preset flow rate, in a series of one ormore pulses, to the 1) organ(s), tissues or vasculature associated withthe organ(s), 2) the body cavity, or 3) cavities of the body. Once thisfluid volume was delivered, the pump could be brought into reverse,either automatically or manually. This reversal would involve a seriesof one or more pulses to extract a volume approximately equivalent tothat which was delivered, or other predetermined volume, back into thereservoir of the device. This cycle could continue for as long asdesired, that is typically until organ harvesting begins (withbrain-dead patients or cadavers), or until body function are restored(with live patients).

Since an organ preservation solution inflow, to the body, and solutionoutflow, back to the reservoir from the body, occurs, double lumencatheters (or multiple lumen catheters) are very useful. Alternately,the pump could be set to pulse only in a forward direction to inject theorgan, peruse the body cavity, or infuse cavities of the body, in anon-cyclic manner.

Additional cooling is achieved by applying external cooling means toportions of the live or brain-dead patient or cadaver proximate to theorgans being treated (in live patients) or to be harvested (as withbrain-dead patients or cadavers. The cooling means include wrapscontaining ice cubes, synthetic cooling packets and the like.

With additional respect to the body cavity perfusion and infusion of thecavities of the body methods, additional circulation of the perfusedorgan preservation solution may be desired. This may be accomplishedwith external compressire garments or devices such as mast trouser-likepneumatic or hydraulic compressive body garments (placable anywherealong the body), or chest thumper type percussion devices, or otherequivalent devices. Additionally, a pneumatic or mechanical device couldbe used to achieve a rocking motion of the body or the body cavity,thereby circulating and stirring the organ preservation solution withinthe body.

In one organ preservation solution, oxygen carrying agents compriseabout 0.000 to 99.900 percent by volume of this organ preservationsolution. The preferred organ preservation solution includes 10.000 to99.000 percent by volume of oxygen carrying agents. Perfluorocarbons arethe preferred oxygen carrying agents, as they have an extremely highoxygen capacity. When delivered to the organ, body cavity, or cavitiesof the body, in this oxygenation step, these perfluorocarbons may besupersaturated with oxygen, either having been oxygenated in the fluidreservoir, or preoxygenated prior to having been placed in thereservoir. These perfluorocarbons act as a blood substitute, carryingoxygen to the organ(s) similar to hemoglobin in the blood. Alternately,these oxygen carrying agents (e.g. perfluorocarbons) could be deliveredto the body in a non-oxygenated state. These perfluorocarbons aretemperature controlled and enter the patient's circulation attemperatures between 0 and 105 degrees F.

Antioxidants comprise from about 0.000 to 50.000 percent by volume ofthis organ preservation solution. Preferably, the organ preservationsolution includes 0.001 to 30.000 percent by volume of antioxidants.These antioxidants are the preferred free radical scavengers. Onceintroduced into the organ(s), these antioxidants compete with organtissue proteins as binding sites for the free radicals, mainly ionic O₂⁻. Since a large portion of the free radicals complex with antioxidants,a substantial amount of free radical damage is prevented since thesesame free radicals do not bind and form complexes with proteins in thetissues forming the organ. The preferred antioxidants include Vitamin A,Vitamin B, Vitamin C, Vitamin E, Selenium, Cystine, Cysteine, BHT, BHA,Hydergine and the like.

Lazaroids, an experimental drug class being developed by the Upjohn Co.of Kalamazoo, Mich., comprise about 0.000 to 30.000 percent by volume ofthe organ preservation solution. Preferably, Lazaroids comprise 0.001 to20.000 percent by volume of the organ preservation solution. TheseLazaroids are the preferred agents for protecting and reversing anoxicinjury for up to forty-five minutes of anoxia, as shown in animalstudies. These Lazaroids, as well as nutrients, are introduced to theorgan(s) as part of preserving the organ(s). Lazaroids are also freeradical scavengers which fall under two major root moieties: pregnanes,ranging in molecular weight from roughly 580-720 and benzopyrans,ranging in molecular weight from 425-905.

The organ preservation solution may include up to 50.000 percent byvolume of components which act as carrier vehicles and diluents for theantioxidants, perfluorocarbons and Lazaroids. Dimethylsulfoxide (DMSO)is the preferred carrier as it aids the above agents in traversingtissue cell membranes. Additionally, the organ preservation solution maycontain physiologic buffers to maintain pH.

Nutrients are also provided in this solution, up to 30.000 percent byvolume. Glucose is one nutrient which is preferred.

The solution may also include up to 20.000 percent by volume heavy metalscavengers or chelating agents. These heavy metal scavengers orchelating agents would also serve to inhibit free radical damage.Desferoxamine is one preferred heavy metal chelator.

Cytoprotective agents such as Calcium Channel Blockers (Ca⁺⁺) may alsobe present in this organ preservation solution in amounts up to 10.000percent by volume. These cytoprotective agents, inhibit cell damage bystabilizing the cell membrane.

Additional metabolic mediators such as MK-801 and glutamate, aspartateor N-methyl-d-aspartate (NMDA) antagonists may also be in the solutionup to 10.000 percent by volume.

Finally, the solution may contain up to 10.000 percent by volume ofheparin or other suitable anti-blood coagulating agents to stop bloodclotting which may occur due to lack of blood flow during the trauma, ordue to the fact the patient is dead.

In another organ preservation solution, oxygen carrying agents compriseabout 0.000 to 99.900 percent by volume of this organ preservationsolution. The preferred organ preservation solution includes 10.000 to99.000 percent by volume of oxygen carrying agents. Perfluorocarbons,hemoglobin based blood substitutes, or non-hemoglobin based bloodsubstitutes are the preferred oxygen carrying agents, as they have anextremely high oxygen capacity. When delivered to the organ, in thisoxygenation step, these oxygen carrying agents may be supersaturatedwith oxygen, either having been oxygenated in the fluid reservoir, orpreoxygenated prior to having been placed in the reservoir. Theseperfluorocarbons, hemoglobin based blood substitutes, or non-hemoglobinbased blood substitutes, act as blood substitutes, carrying oxygen tothe organ(s) similar to hemoglobin in the blood. Alternately, theseoxygen carrying agents (e.g. perfluorocarbons, hemoglobin based bloodsubstitutes, or non-hemoglobin based blood substitutes) could bedelivered to the body in a non-oxygenated state. These perfluorocarbons,hemoglobin based blood substitutes, or non-hemoglobin based bloodsubstitutes are temperature controlled and enter the patient'scirculation at temperatures between 0 and 105 degrees F.

Antioxidants comprise from about 0.000 to 50.000 percent by volume ofthis organ preservation solution. Preferably, the organ preservationsolution includes 0.001 to 30.000 percent by volume of antioxidants.These antioxidants are the preferred free radical scavengers. Onceintroduced into the organ(s), these antioxidants compete with organtissue proteins as binding sites for the free radicals. Since a largeportion of the free radicals complex with antioxidants, a substantialamount of free radical damage is prevented since these same freeradicals do not bind and form complexes with proteins in the tissuesforming the organ. The preferred antioxidants include Vitamin A, VitaminB, Vitamin C, Vitamin E, Selenium, Cystine, Cysteine, BHT, BHA,Hydergine and the like.

The organ preservation solution may include up to 99.000 percent byvolume of components which act as carrier vehicles and diluents for theantioxidants and oxygen carrying agents (e.g., perfluorocarbons orhemoglobin based blood substitutes, or non-hemoglobin based bloodsubstitutes). Dimethylsulfoxide (DMSO) or Normosol® (AbbottLaboratories, North Chicago, Ill.) are the preferred carriers as theyaid the above agents in traversing tissue cell membranes.

Additionally, the organ preservation solution may contain physiologicbuffers, such as HEPES (Monograph No. 4573, The Merk Index, EleventhEdition) in amounts up to 50.000 percent by volume, to maintain pH.

Nutrients are also provided in this solution, up to 30.000 percent byvolume. Glucose is one nutrient which is preferred.

The solution may also include up to 20.000 percent by volume heavy metalscavengers or chelating agents. These heavy metal scavengers orchelating agents would also serve to inhibit free radical damage.Desferoxamine is one preferred heavy metal chelator.

Cytoprotective agents such as Calcium Channel Blockers (Ca⁺⁺) may alsobe present in this organ preservation solution in amounts up to 10.000percent by volume. These cytoprotective agents, inhibit cell damage bystabilizing the cell membrane.

Ionotropic agents, such as epinephrine and dopamine, may be present inthis solution up to 5.000 percent by volume.

Electrolytes, such as magnesium chloride, may be present in thissolution up to 10.000 percent by volume.

Additional metabolic mediators such as MK-801 and glutamate, aspartateor N-methyl-d-aspartate (NMDA) antagonists may also be in the solutionup to 10.000 percent by volume.

Finally, the solution may contain up to 10.000 percent by volume ofheparin or other suitable anti-blood coagulating agents to stop bloodclotting which may occur due to lack of blood flow during the trauma, ordue to the fact the patient is brain-dead or a cadaver.

In brain-dead patients and cadavers, once these methods have beenperformed and the organ preservation solution has been properlyadministered, organ harvesting may begin. With respect to live patients,these methods may be performed as long as necessary until the trauma iscontrolled (e.g. the heart is restarted, body functions are restored) orother medical treatment is begun.

From the foregoing description, it is clear that those skilled in theart could make changes in the described embodiments and methods of theinvention without departing from the broad inventive concepts thereof.It is understood, therefore, that this invention is not limited to theparticular embodiments disclosed, but it is intended to cover anymodifications which are within the spirit and scope of the claims.

What is claimed is:
 1. A method of treating tissues and/or organs in alive patient or cadaver comprising:a) accessing a body cavity of thepatient or cadaver; and b) perfusing the body cavity of the patient orcadaver by:1) lowering the temperature of the organs in the body cavity,by introducing cooled fluid into the accessed body cavity, said cooledfluid being at a temperature below body temperature; 2) inhibiting freeradical damage in the organs by introducing a free radical scavengerinto the accessed body cavity; and 3) oxygenating said organs byintroducing an oxygen carrying agent into the accessed body cavity,whereby the metabolic rates of said tissues and/or said organs areslowed and said tissues and/or said organs remain viable.
 2. The methodof claim 1, wherein said method further includes the step of introducinga tissue-protecting agent and a damage-reversing agent into the accessedbody cavity.
 3. The method of claim 1, wherein said oxygen carryingagent is selected from the group consisting of perfluorocarbons,hemoglobin based blood substitutes and non-hemoglobin based bloodsubstitutes.
 4. The method of claim 1, wherein said fluid isapproximately 40 degrees F.
 5. The method of claim 1, additionallycomprising the step of externally compressing the body of said livepatient or cadaver proximate the body cavity.
 6. The method of claim 1,wherein said free radical scavenger is selected from the groupconsisting of antioxidants.
 7. The method of claim 6, wherein saidantioxidant is selected from the group consisting of Vitamin A, VitaminB, Vitamin C, Vitamin E, Selenium, Cystine, Cysteine, BHT, BHA andHydergine.
 8. The method of claim 1, wherein accessing the body cavityof the patient or cadaver includes instrumentizing the body cavity bypiercing the skin.
 9. The method of claim 8, wherein saidinstrumentizing the body cavity includes cannulating the body cavity.10. A method of treating tissues and/or organs in a live patient orcadaver comprising:a) accessing a cavity of the body of the patient orcadaver; and infusing the cavity of the body of the patient or cadaverby:1) lowering the temperature of the organs in the body cavity, byintroducing cooled fluid into the accessed cavity of the body, saidcooled fluid being at a temperature below body temperature; 2)inhibiting free radical damage in the organs by introducing a freeradical scavenger into the accessed cavity of the body; and 3)oxygenating said organs by introducing an oxygen carrying agent into theaccessed cavity of the body, whereby the metabolic rates of said tissuesand/or said organs are slowed and said tissues and/or said organs remainviable.
 11. The method of claim 10, wherein said cavity of the body isselected from the group consisting of the gastro-intestinal tract, therespiratory tract and the urinary tract.
 12. The method of claim 10,wherein said method further includes the step of introducing atissue-protecting agent and a damage-reversing agent into the accessedcavity of the body.
 13. The method of claim 10, wherein said oxygencarrying agent is selected from the group consisting ofperfluorocarbons, hemoglobin based blood substitutes and non-hemoglobinbased blood substitutes.
 14. The method of claim 10, wherein said fluidis approximately 40 degrees F.
 15. The method of claim 10, additionallycomprising the step of externally compressing the body of said livepatient or cadaver proximate the cavity of the body.
 16. The method ofclaim 10, wherein said free radical scavenger is selected from the groupconsisting of antioxidants.
 17. The method of claim 16, wherein saidantioxidant is selected from the group consisting of Vitamin A, VitaminB, Vitamin C, Vitamin E, Selenium, Cystine, Cysteine, BHT, BHA andHydergine.
 18. The method of claim 11, wherein accessing the cavity ofthe body of the patient or cadaver includes instrumentizing the cavityof the body at a body orifice.
 19. The method of claim 18, wherein saidinstrumentizing the cavity of the body includes cannulating the bodyorifice.
 20. A method of treating living tissue in mammals comprising:a)providing a biocompatible solution, said solution comprising aneffective amount of a free radical scavenger for inhibiting free radicaldamage and an effective amount of an oxygen carrying agent fortransporting oxygen to said tissue; b) bringing said biocompatiblesolution to a temperature substantially below body temperature; and c)perfusing said biocompatible solution into a body cavity of said mammal.21. The method of claim 20, wherein said oxygen carrying agent isselected from the group consisting of perfluorocarbons, hemoglobin basedblood substitutes and non-hemoglobin based blood substitutes.
 22. Themethod of claim 20, wherein said solution is approximately 40 degrees F.23. The method of claim 20, additionally comprising the step ofretrieving said biocompatible solution from said body cavity.
 24. Themethod of claim 20, wherein said free radical scavenger is selected fromthe group consisting of antioxidants.
 25. The method of claim 24,wherein said antioxidant is selected from the group consisting ofVitamin A, Vitamin B, Vitamin C, Vitamin E, Selenium, Cystine, Cysteine,BHT, BHA and Hydergine.
 26. The method of claim 20, wherein saidperfusing said biocompatible solution into said body cavity of saidmammal includes the step of instrumentizing said body cavity of saidmammal.
 27. The method of claim 26, wherein said instrumentizing stepincludes piercing the skin of said mammal.
 28. The method of claim 26,wherein said instrumentizing step includes cannulation of said mammal.29. A method of treating living tissue in mammals comprising:a)providing a biocompatible solution, said solution comprising aneffective amount of a free radical scavenger for inhibiting free radicaldamage and an effective amount of an oxygen carrying agent fortransporting oxygen to said tissue; b) bringing said biocompatiblesolution to a temperature substantially below body temperature; and c)infusing said biocompatible solution into at least one cavity of thebody of said mammal.
 30. The method of claim 29, wherein said cavity ofthe body of said mammal is selected from the group consisting of thegastro-intestinal tract, the respiratory tract and the urinary tract.31. The method of claim 29, wherein said oxygen carrying agent isselected from the group consisting of perfluorocarbons, hemoglobin basedblood substitutes and non-hemoglobin based blood substitutes.
 32. Themethod of claim 29, additionally comprising the step of retrieving saidbiocompatible solution from said cavity of the body.
 33. The method ofclaim 29, wherein said free radical scavenger is selected from the groupconsisting of antioxidants.
 34. The method of claim 33, wherein saidantioxidant is selected from the group consisting of Vitamin A, VitaminB, Vitamin C, Vitamin E, Selenium, Cystine, Cysteine, BHT, BHA andHydergine.
 35. The method of claim 29, wherein said solution isapproximately 40 degrees F.
 36. The method of claim 29, wherein saidinfusing said biocompatible solution into said cavity of the body ofsaid mammal includes the step of instrumentizing said cavity of the bodyof said mammal at a body orifice.
 37. The method of claim 36, whereinsaid instrumentizing step includes cannulation of said mammal.